Cytoskeleton and Signaling Pathways in Photoreceptors

光感受器具有复杂的细胞骨架，可能调节光敏感的形态发生 细胞器，当然还有直接的蛋白质和囊泡运输。在其他细胞中控制细胞骨架组织的信号通路已经被确定。在光感受器中，最已知的信号通路是涉及G蛋白偶联受体视紫红质的光转导。我们认为，视紫红质对光的吸收影响了与光转导平行运行的其他信号转导途径，并导致已描述的光感受器的形态变化和视网膜蛋白质的重新定位。此外，我们认为这些观察到的变化是由细胞骨架指导的，细胞骨架的组织由视紫红质功能开启和关闭的信号通路控制。我们认为 Rho GTPase信号通路受视紫红质活性的影响，并控制光感受器中细胞骨架的整体组织；视紫红质的激活招募信号通路，导致细胞骨架蛋白和其他可能与细胞骨架相互作用的蛋白质的mRNA表达发生变化；以及这些细胞骨架蛋白中的一些蛋白质的mRNA在需要时在光或黑暗中存储和翻译。为了验证我们的假设，我们将追求以下具体目标：1)光调节光感受器中影响肌动蛋白分布的Rho信号通路；2)光调节光感受器中特定细胞骨架mRNAs的表达并将其翻译成蛋白质；3)光感受器中特定细胞骨架mRNAs处于休眠状态，直到在适当的光照条件下转换。我们的模型系统将是章鱼光感受器，它体积大，易于操作，并有助于免疫细胞化学、分子和生化研究，旨在阐明光对视网膜细胞骨架组织的影响。我们有初步证据支持每个特定目标的追求，它们的完成将极大地促进我们对光如何影响细胞骨架组织和基因表达光感受器的理解，以及对控制这一组织的分子途径的理解。对视网膜信号通路的了解将有助于我们理解涉及细胞骨架蛋白的视网膜疾病。

Photoreceptors have complex cytoskeletons that may regulate morphogenesis of light sensitive organelles and certainly direct protein and vesicular trafficking. Signaling pathways that control cytoskeletal organization in other cells have been identified. In photoreceptors, the best known signaling pathway is phototransduction involving the G-protein coupled receptor rhodopsin. We believe that the absorption of light by rhodopsin affects other signal transduction pathways, which run in parallel with phototransduction, and lead to morphological changes in photoreceptors and relocation of retinal proteins that have been described. Furthermore, we believe that these observed changes are directed by the cytoskeleton whose organization is controlled by signaling pathways switched on and off by rhodopsin function. We think that Rho GTPase signaling pathways are affected by rhodopsin activity and control the overall organization of the cytoskeleton in photoreceptors; that activation of rhodopsin recruits signaling pathways leading to changes in mRNA expression of cytoskeletal proteins and other proteins that may interact with the cytoskeleton; and that mRNA for some of these cytoskeletal proteins is stored and translated when needed in either the light or dark. To test our assumptions we will pursue the following Specific Aims: 1) light regulates a Rho signaling pathway in photoreceptors that affects actin distribution; 2) light regulates the expression of specific cytoskeletal mRNAs in photoreceptors and their translation into protein; and 3) specific cytoskeletal mRNAs in photoreceptors are dormant until translation in the appropriate lighting condition. Our model system will be octopus photoreceptors which are large and easy to manipulate and facilitate immunocytochemical, molecular and biochemical studies aimed at elucidating the effects of light on retinal cytoskeletal organization. We have preliminary evidence to support the pursuit of each specific aim and their completion will significantly advance our understanding of how light affects cytoskeletal organization and gene expression photoreceptors and to the understanding of molecular pathways that control this organization. Knowledge of retinal signaling pathways will facilitate our understanding of retinal diseases that involve cytoskeletal proteins.